Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)

HIV Infection Clinical Trial

Official title:

A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04223778
• Other study ID #: 8591A-017
• Secondary ID: MK-8591A-0172051
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 18, 2020
• Est. completion date: November 22, 2024

Study information

• Verified date: March 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified background antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 672
• Est. completion date: November 22, 2024
• Est. primary completion date: September 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Is HIV-1 positive

• Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for =3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.

• Female is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive

Exclusion Criteria:

• Has HIV-2 infection

• Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator

• Has an active diagnosis of hepatitis due to any cause, including active Hepatitis B Virus (HBV) co-infection

• Has a history of malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma

• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies

• Is currently taking long-acting cabotegravir-rilpivirine

• Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period

• Has a documented or known virologic resistance to DOR

• Female expects to conceive or donate eggs at any time during the study

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• DOR/ISL
A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily
• ART
Baseline background ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters.

Locations

Country	Name	City	State
Australia	Melbourne Sexual Health Centre ( Site 2305)	Carlton	Victoria
Australia	Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 2309)	Herston	Queensland
Australia	Fiona Stanley Hospital ( Site 2301)	Murdoch	Western Australia
Australia	Holdsworth House Medical Practice ( Site 2300)	Sydney	New South Wales
Canada	Southern Alberta HIV Clinic ( Site 1108)	Calgary	Alberta
Canada	Hamilton Health Sciences ( Site 1103)	Hamilton	Ontario
Canada	Clinique de Medecine Urbaine du Quartier Latin ( Site 1104)	Montreal	Quebec
Canada	Clinique Medicale L Actuel ( Site 1114)	Montreal	Quebec
Canada	Maple Leaf Research ( Site 1112)	Toronto	Ontario
Canada	Toronto General Hospital - University Health Network ( Site 1105)	Toronto	Ontario
Canada	Vancouver ID Research and Care Centre Society ( Site 1100)	Vancouver	British Columbia
Chile	Centro de Investigacion Clinica UC CICUC ( Site 1303)	Santiago	Region Metropolitana De Santiago
Chile	Clinica Arauco Salud ( Site 1300)	Santiago	Region Metropolitana De Santiago
Chile	Hospital Dr. Hernan Henriquez Aravena ( Site 1305)	Temuco	Araucania
Colombia	Fundacion Valle del Lili ( Site 1201)	Cali	Valle Del Cauca
France	CHU de Bordeaux- Hopital Saint Andre ( Site 2015)	Bordeaux	Gironde
France	Hopital Francois Mitterrand ( Site 2019)	Dijon	Cote-d'Or
France	Hopital de la Croix-Rousse ( Site 2027)	Lyon	Rhone-Alpes
France	CHU Hotel Dieu Nantes ( Site 2020)	Nantes	Loire-Atlantique
France	A.P.H. Paris, Hopital Saint Louis ( Site 2014)	Paris
France	CHU de Rouen ( Site 2005)	Rouen	Seine-Maritime
France	CHU de Toulouse - Hopital Purpan ( Site 2004)	Toulouse	Haute-Garonne
Italy	ASST Fatebenefratelli-Ospedale Sacco ( Site 2200)	Milano
Italy	A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 2208)	Napoli
Italy	Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 2206)	Roma
Japan	National Hospital Organization Nagoya Medical Center ( Site 2403)	Nagoya	Aichi
Japan	National Hospital Organization Osaka National Hospital ( Site 2402)	Osaka
Japan	Center Hospital of the National Center for Global Health and Medicine ( Site 2401)	Tokyo
Japan	Tokyo Medical University Hospital ( Site 2404)	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital ( Site 2406)	Tokyo
New Zealand	Christchurch Hospital ( Site 2303)	Christchurch	Canterbury
Poland	Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 1503)	Lodz-Baluty	Lodzkie
Poland	SP ZOZ Wojewodzki Szpital Zakazny ( Site 1505)	Warszawa	Mazowieckie
Poland	EMC Instytut Medyczny SA Przychodnia przy ul. Lowieckiej we Wroclawiu ( Site 1500)	Wroclaw	Dolnoslaskie
Poland	Wroclawskie Centrum Zdrowia SP ZOZ ( Site 1507)	Wroclaw
Russian Federation	Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 1707)	Kazan	Tatarstan, Respublika
Russian Federation	Kemerovo Regional Center for the Prevention and Control of AIDS ( Site 1713)	Kemerovo	Kemerovskaya Oblast'
Russian Federation	Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 1712)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	Federal Scientific Methodological AIDS Prevention and Control Center ( Site 1703)	Moscow	Moskva
Russian Federation	Infectious Clinical Hospital #2 ( Site 1719)	Moscow	Moskva
Russian Federation	FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 1700)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 1701)	Saint Petersburg	Leningradskaya Oblast'
Russian Federation	Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 1715)	Yekaterinburg	Sverdlovskaya Oblast'
South Africa	JOSHA Research ( Site 1406)	Bloemfontein	Free State
South Africa	Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 1414)	Cape Town	Western Cape
Spain	Hospital Universitari Germans Trias i Pujol ( Site 1606)	Badalona	Barcelona [Barcelona]
Spain	Hospital Clinic i Provincial ( Site 1600)	Barcelona
Spain	Hospital General de Elche ( Site 1608)	Elche	Alicante
Spain	Hospital General Universitario Gregorio Maranon ( Site 1603)	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz ( Site 1602)	Madrid
Spain	Hospital Universitario Infanta Leonor ( Site 1601)	Madrid
Spain	Hospital Universitario La Paz ( Site 1604)	Madrid
Switzerland	Universitaetsspital Basel ( Site 3302)	Basel	Basel-Stadt
Switzerland	Inselspital Universitaetsspital Bern ( Site 3303)	Bern	Berne
Switzerland	Hopitaux Universitaires de Geneve HUG. ( Site 3304)	Geneva	Geneve
Switzerland	Ospedale Regionale di Lugano Civico ( Site 3305)	Lugano	Ticino
Switzerland	Kantonsspital St. Gallen ( Site 3301)	St. Gallen	Sankt Gallen
Switzerland	Universitaetsspital Zuerich ( Site 3300)	Zuerich	Zurich
United Kingdom	Brighton and Sussex University Hospital NHS Trust ( Site 1908)	Brighton	Brighton And Hove
United Kingdom	Southmead Hospital ( Site 1910)	Bristol	Bristol, City Of
United Kingdom	Kings College Hospital NHS Foundation Trust ( Site 1907)	London	London, City Of
United Kingdom	Royal Free Hospital ( Site 1904)	London	Camden
United Kingdom	North Manchester General Hospital ( Site 1902)	Manchester
United States	Saint Hope Foundation, Inc. ( Site 1037)	Bellaire	Texas
United States	University of North Carolina at Chapel Hill ( Site 1042)	Chapel Hill	North Carolina
United States	Northstar Healthcare ( Site 1002)	Chicago	Illinois
United States	North Texas ID Consultants, PA ( Site 1003)	Dallas	Texas
United States	Midway Immunology and Research ( Site 1030)	Fort Pierce	Florida
United States	Texas Centers for Infectious Disease Associates P.A. ( Site 1022)	Fort Worth	Texas
United States	ID Care ( Site 1023)	Hillsborough	New Jersey
United States	The Crofoot Research Center, Inc. ( Site 1005)	Houston	Texas
United States	Kansas City CARE Health Center ( Site 1008)	Kansas City	Missouri
United States	Bliss Healthcare Services ( Site 1025)	Orlando	Florida
United States	Orlando Immunology Center ( Site 1007)	Orlando	Florida
United States	University of Pennsylvania ( Site 1038)	Philadelphia	Pennsylvania
United States	Chatham County Health Department ( Site 1043)	Savannah	Georgia
United States	Georgetown University Hospital ( Site 1018)	Washington	District of Columbia
United States	Triple O Research Institute, P.A. ( Site 1026)	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  Colombia,  France,  Italy,  Japan,  New Zealand,  Poland,  Russian Federation,  South Africa,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) =50 Copies/mL at Week 48	HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA =50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.	Week 48
Primary	Percentage of Participants With One or More Adverse Events (AEs) up to Week 48	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE was reported.	Up to ~48 Weeks
Primary	Percentage of Participants Who Discontinued Study Intervention up to Week 48	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE was reported.	Up to ~48 Weeks
Secondary	Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48	HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL or <50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA =50 Copies/mL, <40 Copies/mL or <50 Copies/mL From Week 48 to Week 96	HIV-1 RNA levels in blood samples taken at each visit will be measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA =50 copies/mL, <40 copies/mL, or <50 copies/mL from Week 48 to Week 96 will be presented using the FDA Snapshot missing data approach.	Weeks 48-96 (up to ~48 weeks)
Secondary	Percentage of Participants With HIV-1 RNA =50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96	HIV-1 RNA levels in blood samples taken at each visit will be measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA =50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.	Week 96
Secondary	Percentage Change From Baseline in CD4+ T-cell Count at Week 48	Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The percentage change from baseline to Week 48 is presented.	Baseline and Week 48
Secondary	Percentage Change From Baseline in CD4+ T-cell Count at Week 96	Plasma CD4+ T-Cell Count will be measured in cells/mm^3 for baseline and 96 weeks. Baseline measurements will be defined as the Day 1 value of each participant. The percentage change from baseline to Week 96 will be presented.	Baseline and Week 96
Secondary	Percentage Change From Week 48 in CD4+ T-cell Count at Week 96	Plasma CD4+ T-Cell Count will be measured in cells/mm^3 for Week 48 and Week 96. The percentage change from Week 48 to Week 96 will be presented.	Week 48 and Week 96
Secondary	Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48	Viral drug resistance is defined as participants with confirmed HIV-1 RNA =400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated drug resistance at Week 48 is presented.	Week 48
Secondary	Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96	Viral drug resistance is defined as participants with confirmed HIV-1 RNA =400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance at Week 96 will be presented.	Week 96
Secondary	Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)	Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.	Baseline and Week 24
Secondary	Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)	Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.	Baseline and Week 24
Secondary	Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens	Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.	Baseline and Week 24
Secondary	Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)	Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.	Baseline and Week 48
Secondary	Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)	Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.	Baseline and Week 48
Secondary	Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens	Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.	Baseline and Week 48
Secondary	Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens)	Baseline measurements were defined as the Day 1 value of each participant. The change from baseline to Week 48 is presented for participants who received InSTI- based regimens.	Baseline and Week 48
Secondary	Percentage of Participants With One or More AEs up to Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.	Up to ~96 Weeks
Secondary	Percentage of Participants Who Discontinued Study Intervention up to Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study intervention due to an AE will be reported.	Up to ~96 Weeks
Secondary	Percentage of Participants With One or More AEs From Week 48 to Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.	Weeks 48-96
Secondary	Percentage of Participants Who Discontinued Study Intervention From Week 48 to Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study intervention due to an AE will be reported.	Weeks 48-96

External Links

•   Merck Clinical Trials Information